Abstract

The long term objectives are to understand the physiological and pathophysiological roles of gastrin in the regulation of gastric acid secretion, to understand the nature and significance of interactions between gastrin and other hormonal and paracrine regulatory peptides that influence parietal cell function, and to understand the regulation of synthesis and secretion of gastrin by gastrin cells. The physiological role of circulating gastrin will be studied by specific immunoneutralization of gastrin by monoclonal antibodies. The potential endocrine and paracrine roles of somatostatin as a peripheral antagonist of gastrin action and of gastrin release will be studied by specific immunoneutralization with IgG and Fab fragments of monoclonal antibodies to somatostatin. Biosynthesis and processing of gastrin will be studied by use of antibodies specific for different regions of the progastrin molecule and by measurement of gastrin mRNA. Release of gastrin by apical and basal lateral stimulants will be studied in an isolated canine gastrin cell preparation. The intracellular mediators of the gastrin response to phenylalanine will be defined. Finally, parallel and nonparallel regulation of gastrin cell proliferation, gastrin synthesis, gastrin processing, and gastrin release will be studied in rats and dogs.

  Funding Agency

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Method to Extend Research in Time (MERIT) Award (R37)
Project #
5R37DK017294-15
Application #
3483187
Study Section
General Medicine A Subcommittee 2 (GMA)
Project Start
1977-02-15
Project End
1992-03-31
Budget Start
1988-04-01
Budget End
1989-03-31
Support Year
15
Fiscal Year
1988
Total Cost
Indirect Cost

  Institution

Name
University of California Los Angeles
Department
Type
Schools of Medicine
DUNS #
119132785
City
Los Angeles
State
CA
Country
United States
Zip Code
90095

  Publications

Slice, Lee W; Chiu, Terence; Rozengurt, Enrique (2005) Angiotensin II and epidermal growth factor induce cyclooxygenase-2 expression in intestinal epithelial cells through small GTPases using distinct signaling pathways. J Biol Chem 280:1582-93
Shin, Jai Moo; Grundler, Gerhard; Senn-Bilfinger, Jorg et al. (2005) Functional consequences of the oligomeric form of the membrane-bound gastric H,K-ATPase. Biochemistry 44:16321-32
Hunger-Glaser, Isabel; Fan, Robert S; Perez-Salazar, Eduardo et al. (2004) PDGF and FGF induce focal adhesion kinase (FAK) phosphorylation at Ser-910: dissociation from Tyr-397 phosphorylation and requirement for ERK activation. J Cell Physiol 200:213-22
Kim, Nayoung; Marcus, Elizabeth A; Wen, Yi et al. (2004) Genes of Helicobacter pylori regulated by attachment to AGS cells. Infect Immun 72:2358-68
Vagin, Olga; Turdikulova, Shahlo; Sachs, George (2004) The H,K-ATPase beta subunit as a model to study the role of N-glycosylation in membrane trafficking and apical sorting. J Biol Chem 279:39026-34
Keire, David A; Vincent Wu, S; Diehl, David L et al. (2003) Rat progastrin processing yields peptides with altered potency at the CCK-B receptor. Regul Pept 113:115-24
Chiu, Terence; Santiskulvong, Chintda; Rozengurt, Enrique (2003) ANG II stimulates PKC-dependent ERK activation, DNA synthesis, and cell division in intestinal epithelial cells. Am J Physiol Gastrointest Liver Physiol 285:G1-11
Wen, Yi; Marcus, Elizabeth A; Matrubutham, Uday et al. (2003) Acid-adaptive genes of Helicobacter pylori. Infect Immun 71:5921-39
Hunger-Glaser, Isabel; Salazar, Eduardo Perez; Sinnett-Smith, James et al. (2003) Bombesin, lysophosphatidic acid, and epidermal growth factor rapidly stimulate focal adhesion kinase phosphorylation at Ser-910: requirement for ERK activation. J Biol Chem 278:22631-43
Yuan, Jingzhen; Slice, Lee W; Gu, Jennifer et al. (2003) Cooperation of Gq, Gi, and G12/13 in protein kinase D activation and phosphorylation induced by lysophosphatidic acid. J Biol Chem 278:4882-91

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